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Literature summary for 5.3.99.2 extracted from

  • Irikura, D.; Aritake, K.; Nagata, N.; Maruyama, T.; Shimamoto, S.; Urade, Y.
    Biochemical, functional and pharmacological characterization of AT-56, an orally active and selective inhibitor of lipocalin-type prostaglandin d synthase (2009), J. Biol. Chem., 284, 7623-7630.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 5.3.99.2

Application

Application Comment Organism
medicine orally administered AT-56, i.e. 4-dibenzo [a,d]cyclohepten-5-ylidene-1-[4-(2H-tetrazol-5-yl)-butyl]-piperidine, below 30 mg/kg body weight decreases the prostaglandin D2 production to 40% in the brain of H-PGDS-deficient mice after a stab-wound injury in a dose-dependent manner without affecting the production of prostaglandin E2 and prostaglandin F2alpha, and also suppresses the accumulation of eosinophils and monocytes in the bronco-alveolar lavage fluid from the antigen-induced lung inflammation model of human L-PGDS-transgenic mice Mus musculus

Protein Variants

Protein Variants Comment Organism
C89A/C186A mutant retains wild-type like activity and is stable Mus musculus
W54A mutant retains wild-type like activity and is stable Mus musculus

Inhibitors

Inhibitors Comment Organism Structure
4-dibenzo [a,d]cyclohepten-5-ylidene-1-[4-(2H-tetrazol-5-yl)-butyl]-piperidine i.e. AT-56, inhibits the activity of lipocalin-type prostaglandin-D synthase in a concentration-dependent manner, but does not affect the activities of hematopoietic prostaglandin-D synthase, cyclooxygenase-1 and -2, and microsomal PGE synthase-1. AT-56 inhibits the lipocalin-type prostaglandin-D synthase activity in a competitive manner against the substrate prostaglandin H2 but does not inhibit the binding of 13-cis-retinoic acid. AT-56 occupies the catalytic pocket, but not the retinoid-binding pocket, of lipocalin-type prostaglandin-D synthase Homo sapiens
4-dibenzo [a,d]cyclohepten-5-ylidene-1-[4-(2H-tetrazol-5-yl)-butyl]-piperidine i.e. AT-56. Orally administered AT-56 below 30 mg/kg body weight decreases the prostaglandin D2 production to 40% in the brain of H-PGDS-deficient mice after a stab-wound injury in a dose-dependent manner without affecting the production of prostaglandin E2 and prostaglandin F2alpha, and also suppresses the accumulation of eosinophils and monocytes in the bronco-alveolar lavage fluid from the antigen-induced lung inflammation model of human L-PGDS-transgenic mice Mus musculus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.014
-
 (5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate pH 8.0 Homo sapiens
0.014
-
 (5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate pH 8.0 Mus musculus

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Mus musculus O09114
-
-

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
 Mus musculus
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
-
 Homo sapiens (5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate
-
 ?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
-
 Mus musculus (5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate
-
 ?

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.075
-
 4-dibenzo [a,d]cyclohepten-5-ylidene-1-[4-(2H-tetrazol-5-yl)-butyl]-piperidine pH 8.0 Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.003
-
 inhibition of enzyme in lipocalin-type prostaglandin-D synthase-expressing TE-671 cells after stimulation with Ca2+-ionophore A23187 Homo sapiens 4-dibenzo [a,d]cyclohepten-5-ylidene-1-[4-(2H-tetrazol-5-yl)-butyl]-piperidine